Centrosome abnormalities are frequently observed in non-small-cell lung cancer and are associated with aneuploidy and cyclin E overexpression

J Pathol. 2006 Aug;209(4):512-21. doi: 10.1002/path.2005.


Centrosome abnormalities are observed in human cancers and have been associated with aneuploidy, a driving force in tumour progression. However, the exact pathways that tend to cause centrosome abnormalities have not been fully elucidated in human tumours. Using a series of 68 non-small-cell lung carcinomas and an array of in vitro experiments, the relationship between centrosome abnormalities, aneuploidy, and the status of key G1 to S-phase transition cell-cycle molecules, involved in the regulation of centrosome duplication, was investigated. Centrosome amplification and structural abnormalities were common (53%), were strongly related to aneuploidy, and, surprisingly, were even seen in adjacent hyperplastic regions, suggesting the possibility that these are early lesions in lung carcinogenesis. Cyclin E and E2F1 overexpression, but not p53 mutation, was observed to correlate with centrosome abnormalities in vivo (p = 0.029 and p = 0.015, respectively). This was further strengthened by the observation that cyclin E was specifically present in the nucleus and/or cytoplasm of the cells that contained centrosome aberrations. The cytoplasmic cyclin E signal may be attributed, in part, to the presence of truncated low-molecular-weight isoforms of cyclin E. In order to isolate the effect of cyclin E on the appearance of centrosome abnormalities, a U2OS tetracycline-repressible cyclin E cell line that has a normal centrosome profile by default was used. With this system, it was confirmed in vitro that persistent cyclin E overexpression is sufficient to cause the appearance of centrosome abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aneuploidy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Centrosome / ultrastructure*
  • Chi-Square Distribution
  • Cyclin E / genetics*
  • E2F1 Transcription Factor / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genes, p53
  • Humans
  • In Situ Hybridization
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Statistics, Nonparametric


  • Cyclin E
  • E2F1 Transcription Factor
  • E2F1 protein, human